Detection of chromium and vanadium is of interest for biomedical and environmental applications. The two metals have narrow limits between being essential and toxic for humans. Ultra-sensitive techniques have been studied to measure Cr and V at low concentrations found in human blood and environmental samples. Bismuth film and mercury-alloy electrodes have been developed as alternatives to traditional Hg-based electrodes for Cr and V detection. While catalytic adsorptive stripping voltammetry (CAdSV) has been used to detect Cr and V, little is known about the process. The mechanisms of CAdSV have been probed to provide a better understanding of its exceptional sensitivity and selectivity. Near-real time monitoring of plume gas constituents is desired as a diagnostic tool for combustion efficiency, ensuring safe testing conditions and observing releases of green house gasses. Ground testing rockets is a crucial preliminary step that ensures their performance during critical space missions. Optical sol-gel sensors for carbon dioxide have been developed for remote sensing applications. They are inexpensive and are compatible with the harsh environments encountered during rocket plume tests. The sensors are a viable approach to compliment current infrared (IR) measurements for real-time carbon dioxide detection. Additional work on kerosene and isopropyl alcohol sensing has been explored for incorporation into a multi-analyte sensing platform.

Polymeric excipients are generally the least well-characterized components of pharmaceutical formulations. The aim of this dissertation work is to facilitate the quality-by-design (QbD) approach to pharmaceutical formulation and manufacturing by evaluating the inter-grade and inter-batch variability of pharmaceutical-grade polymeric excipients. Sodium alginate, a widely used polymeric excipient, was selected for evaluation using appropriate analytical methods and test conditions, especially rheological methods. The materials used were six different grades of sodium alginate and an additional ten batches of one of the grades. <br>To compare the six grades, steady shear measurements were conducted on solutions at 1, 2, and 3% w/w, consistent with their use as thickening or binding agents. Small amplitude oscillation (SAO) measurements were conducted on sodium alginate solutions at higher concentrations (4-13% w/w) corresponding to their use in controlled release matrices. In order to compare the ten batches of one grade, steady shear and SAO measurements were performed on their solutions at 2% w/w and 8% w/w, respectively. Results show that rheological properties of sodium alginate solutions are influenced by both molecular weight and chemical composition of sodium alginate. ¡§One-point¡¨ apparent viscosity data obtained at one low concentration and one shear rate is not representative of the complex rheological behavior of various grades of sodium alginate solutions at higher concentrations or other shear rates. The potential interchangeability of these different grades used as thickening or binding agents could be established by comparing the apparent viscosities of their solutions as a function of both alginate concentration and shear conditions. For sodium alginate used in controlled release formulations, both steady shear (at one low concentration, e.g., 2% w/w) and SAO measurements (at one high concentration indicative of polymer gel state, e.g., 8% w/w) are recommended to be performed on sodium alginate solutions to ensure interchangeability. Furthermore, among batches of the same grade, significant differences in rheological properties were observed, especially at the high solution concentration (i.e., 8% w/w). In summary, inter-grade and inter-batch variability of sodium alginate can be determined using steady shear and SAO methods. <br>The influence of inter-grade and inter-batch variability of sodium alginate on the functionality of sodium alginate used in matrix tablets was investigated with a focus on compression properties, swelling, erosion behavior of alginate matrix tablets, and drug release from matrix tablets. The compression behavior of four grades and three batches of sodium alginate were studied by compaction energetics, out-of-die Gurnham, and out-of-die Heckel analysis. It was found that sodium alginates deform less plastically than microcrystalline cellulose (MCC PH102) but similar to lactose anhydrous. Sodium alginates also demonstrate more elastic deformations during compression than both MCC PH102 and lactose anhydrous. Compacts prepared from multiple batches of the same grade varied in porosity. The same tensile strength of compacts can be achieved by compressing the multiple batches to the same porosity. <br>Sodium alginate tablets undergo both swelling and erosion in water. Grades with substantially higher apparent viscosities at low solution concentration exhibit a higher percentage of water uptake and a low percentage of erosion. Those batches not significantly different in their apparent viscosities at low solution concentration but significantly different in viscoelasticity at high solution concentrations do demonstrate significant differences in their swelling and erosion behavior. Acetaminophen release from sodium alginate matrix tablets prepared from the four grades and three batches can be well described by a zero-order equation. Significant differences in release profile were observed among various grades and batches. <br>In conclusion, the inter-grade and inter-batch variability of sodium alginate has a significant influence on the swelling, erosion, and drug release behavior of sodium alginate matrix tablets. Apparent viscosities of sodium alginate solution at low concentration alone are not sufficient to predict the functionality of sodium alginate used in matrix tablets. Viscoelastic properties of sodium alginate solutions at high concentrations indicative of polymer gel state are appropriate to be characterized. <br>Further study was conducted to determine whether sodium alginate solutions¡&brkbar; rheological parameters are relevant to sodium alginate¡&brkbar;s use in the formulation of calcium alginate gels. Among the grades with similar guluronic acid percentage (%G), there is a significant correlation between gel fracture force and apparent viscosity. However, the results for the partial correlation analysis for all six grades of sodium alginate show that gel fracture force is significantly correlated with %G, but not with the rheological properties of the sodium alginate solutions. Studies of the ten batches of one grade of sodium alginate show that apparent viscosities of their solutions do not correlate with gel fracture force while tan <em>f</em>Ô values are significantly, but minimally, correlated to gel fracture force. Inter-batch differences in the rheological behavior for one specific grade of sodium alginate are insufficient to predict the corresponding calcium alginate gel's mechanical properties. <br>In summary, rheological methods, including steady shear and small amplitude oscillation, are able to identify the inter-grade and inter-batch variability of sodium alginate. Inter-grade and inter-batch variability of sodium alginate could lead to substantial differences in the functionality of sodium alginate in matrix tablets and in calcium alginate gels. Rheological properties of sodium alginate in solution are suggestive of its functionality as thickeners, or as controlled release agent. However, rheological properties of sodium alginate in solution do not seem to be sufficient to predict the mechanical properties of the corresponding calcium alginate gels. / Mylan School of Pharmacy and the Graduate School of Pharmaceutical Sciences / Pharmaceutics / PhD / Dissertation

Interactions between light and a molecule can result in reversible or irreversible changes in properties of both the light and the molecule. Of the many known interactions, nonlinear absorption is a process in which an intense light signal, for instance from a laser, can be moderated. This can be manifested either in a marked lowering of the light’s intensity or in reductions in fluctuations of its intensity. Such an effect is often termed ‘optical power limiting’ (OPL). High power lasers can be very dangerous since their high intensity can damage or destroy eyes and optical sensors. However, there are currently no adequate protective measures against lasers that cover the entire visible region and there is an increasing demand for new or improved OPL materials. Some of the most promising optical power limiting materials are substances that combine nonlinear optical properties with high transparency in normal light, but after activation by a laser beam, their light transmittance falls extremely rapidly via so-called self-activating mechanisms. The platinum(II) acetylides comprise one class of compounds with such properties. In this study, various OPL Pt(II) acetylides were synthesized and their nonlinear optical properties were characterized. The emphasis of the work was on preparation of the compounds, but in order to design organoplatinum chromophores for OPL, attempts were also made to obtain insight into the mechanisms of nonlinear absorption. The work was divided into two main parts. In the first the goal was to find compounds that are good optical limiters in solution. The possibility of isolating the chromophore site by dendron shielding and the effects of incorporating a thiophene ring into the organic molecular system were also explored. In addition, a new route for synthesizing these compounds was developed. The second part was focused on incorporating the most interesting compounds into solid materials. The preparation and characterization of Pt(II) acetylides with molecular groups for covalent attachment to a silica matrix via the solution gel approach is described.

Nanoparticles (NPs) are often synthesized in organic solvents due to advantages of superior size and shape control obtainable in a non-polar environment. However, many applications featuring NPs require them to be in aqueous media. To transfer NPs from oil to water, surfactants with amphiphilic (hydrophobic and hydrophilic) groups have been widely used. A popular phase-transfer approach involves formation of oil-in-water emulsions upon which the oil storing the NPs is boiled off. In the process, surfactants form bilayers with hydrophobic groups on the NPs rendering them water-dispersible. This transfer route however is limited in that NPs aggregate to form clusters which results in poor colloidal stability and for the specific case of quantum dots (QDs), adversely impacts optical properties. It has ever since remained a challenge to devise approaches that transfer NPs from oil to water as single particles without compromising NP stability and properties. We have discovered that by simple addition of salt to water during the step of emulsion formation, NP transfer efficiency can be greatly enhanced in "salty-micelles" of surfactants. The strength of this approach lies in its simplicity and generic nature in that the transfer scheme is valid for different NP, surfactant and salt types. Using a model system with cadmium selenide (CdSe) QDs as NPs, Aerosol-OT (AOT) as the surfactant and NaCl as the salt in water, we found >90% of CdSe QDs transferred in salty-micelles of AOT which was significantly higher than the 45-55% QDs that transferred in deionized-water (DI-water) micelles of AOT. In the salty-micelle environment, QDs were found to exist predominantly as single NPs with narrow size distribution, as established by light scattering, analytical ultracentrifugation and electron microscopy. The effects of salt were in lowering aqueous solubility of AOT through "salting-out" action and in screening repulsions between like-charged head groups of AOT molecules. Electrophoresis, thermogravimetric analysis and photoluminescence measurements using a solvatochromic dye established higher surfactant coverage with greater lateral compaction for QDs in salty-micelles over the DI-micelle counterpart. Single NP characteristics along with a hydrophobic environment in laterally compact salty-micelles resulted in better retention of optical properties of QDs. Observations of a secondary effect by salt in inducing spontaneous emulsification of a hydrocarbon (octane)/AOT/brine system were systematically investigated by tracking time-variant octane droplet size and charge. Salinity levels that determine the spontaneous curvature and phase behavior of AOT were seen to influence the initial nucleation of octane droplets and their subsequent growth. The smallest octane drops (sub 50 nm) were nucleated at the optimum cross-over salinity and emergence of the liquid crystalline phase of AOT resulted in slowest growth rates. These factors contributed towards higher transfer efficiency of NPs in salty-micelles. Two applications from formulating aqueous NP suspensions by the new phase-transfer approach are described. In the first, QD and carbon-dot (C-Dot) "nanoreporters" were formulated for oil-field reservoir characterization using Neodol 91-7 (nonionic) and Avanel S150 CGN (hybrid nonionic and anionic) as surfactants. These NPs were stable to aggregation under reservoir-representative conditions (salinities: 1M NaCl, 1M KCl and 0.55M synthetic seawater; temperatures: 70-100 °C) and demonstrated flow and transport through crushed-calcite and quartz-sand columns with high breakthrough and recovery (> 90%). In the second application, tandem assembly of a cationic polymer, multivalent salt, and NPs was investigated in a microfluidic channel where charge ratio of the polymer/salt and shear from flow and device geometry determined their assembly into higher ordered structures such as gels and capsules.

With respect to the principles of biomineralization, it is of interest to study the crystallization of calcium oxalates under various experimental conditions. Calcium oxalates play decisive roles as biominerals in plants and as pathological “urinary/kidney stones” in vertebrates. Calcium oxalate exists in three different hydration states; calcium oxalate monohydrate (COM, monoclinic, a = 6.290(1)Å, b = 14.583(1)Å, c = 10.116(1)Å, β = 109.46°, P21/c), calcium oxalate dihydrate (COD, tetragonal, a = b = 12.371(3)Å, c = 7.357(2)Å, α = β = γ = 90°, I4/m) and calcium oxalate trihydrate (COT, triclinic, a = 6.11(1)Å, b = 7.167(2)Å, c = 8.457(2)Å, α = 76.5(2)°, β = 70.35(2)°, γ = 70.62(2)°, P ). Monoclinic COM and tetragonal COD are the most common phyto-crystals and the main constituents of kidney and urinary stones. The occurrence of calcium oxalates in plants represents a useful biogenesis (protection against herbivores) unlike the devastating occurrence in renal tubules. Therefore, biomineralization can be physiological or pathological. A systematic investigation of the morphological evolution of calcium oxalates in the presence of organic components is essential for understanding the mechanism of “pathological biomineralization”. In order to understand the pathological biomineralization of uroliths, it is necessary grow calcium oxalates comparable in morphology under similar growth conditions. The formation of calcium oxalate stones within a gelatinous state of proteins, polysaccharides, lipids and other biomacromolecules under a flow of supersaturated urine supports the fact that an “organic” gel model can simulate the process of urinary stone formation under in vitro conditions. Furthermore, synthetic polymers with precisely known functions and solution behaviours are better choices to understand the interaction of acidic proteins with calcium oxalates. Therefore, as a first step to unravel the complex pathology of uro/nephro lithiasis, we started to examine the structure and morphology of calcium oxalates crystallized in the presence of organic additives such as the sodium salt of polyacrylic acid (PAA) as well as agar gel. The influence of initial calcium oxalate concentration, pH and concentration of the additives on the formation of hydration states of calcium oxalates have been investigated along with the stated general methods. Apart from the three hydrated forms, calcium oxalate exists also in the anhydrous form (COA). Although three modifications of COA (α, β and γ) are reported in the literatures, the crystal structures and phase transformations were controversially discussed. We have been able to reveal the crystal structure of the β-modification of the anhydrous calcium oxalate by a combination of atomistic simulations and Rietveld refinements on the basis of powder X-ray diffraction pattern. β-COA belongs to the monoclinic system with unit cell parameters, a = 6.1644(3)Å, b = 7.3623(2)Å, c = 9.5371(5)Å, β = 90.24(2)°, P2/m (No. 10). The dehydration of COM was mimicked in silico to receive an initial model of the crystal structure of anhydrous calcium oxalate. This general approach may also be accessible for other decomposition processes ending up with crystalline powders of unknown crystal structure. No evidence for transformations from or to the α- or γ- modifications was found during our investigations. The growth pattern of COD crystals precipitated from aqueous solutions in the presence of PAA is clearly dependent on the concentration of PAA. By increasing the concentration of PAA, the shape of COD has been found to change from tetragonal bi-pyramids with dominant (101) pyramidal faces to tetragonal prisms with dominant (100) prism faces and finally to dumbbells. At still higher PAA concentrations, the morphology is reverted back to rod-like tetragonal prisms. Apart from these experiments, the interaction of PAA with (100) and (101) crystal faces of COD was explored with the aid of atomistic simulations. The simulation confirmed that during the development of the aggregates, strong interactions of PAA with the (100) faces take over control of morphologies. Our investigations show that the inner architecture of all the morphological varieties of COD was found to be dominated by an inner “core” consisting of thin elongated crystallites together with incorporated PAA and an outer “shell” formed as a consequence of secondary nucleation processes. We propose that for all types of COD aggregates, relative proportion of calcium oxalate and PAA dictates the shape and formation of nanometer sized crystallites which then aggregate and align to form the core. Such cores enriched with PAA may act as the sites for secondary nucleation events of calcium oxalate crystallites which then cover the core like a shell. In vitro experimental models for the growth of calcium oxalates can give valuable information on the growth and aggregation of urinary stones. Therefore, the “double diffusion technique” in agar gel matrix has been used for the biomimetic growth of calcium oxalate (COM) stones. A great variety of morphological forms of COM are produced in agar gel matrices (2 wt.-% agar gel of pH 8.5) ranging from platy crystallites to dumbbells and spherulites. The COM dumbbells and spherulites are assumed to be formed by the aggregation of smaller crystallites as a consequence of increased supersaturation inside the gel. Moreover, an increase of the pH value of the agar gel has been found to suppress the growth of COM and favours the growth of COD. The morphology of COD crystals grown in 2 wt.-% agar gel of pH 11.5 includes tetragonal prisms and dumbbells. The system calcium oxalate/ PAA/ H2O is a suitable model system for the investigation of principles of biomineral growth (shape development) in general. Our results demonstrate that the double diffusion technique in agar gel is a convenient route to grow calcium oxalate aggregates showing close resemblance to biogenic calculi and to study their ontogeny.

Ce travail présente la préparation et la caractérisation de matériaux hybrides organiques<br />inorganiques pour applications en la photonique. La théorie associée à la préparation des<br />matériaux est décrite et quelques résultats d'autres travaux déjà publiés concernant ces<br />matériaux sont présentés. La structure du matériau obtenu après hydrolyse et condensation est<br />détaillée en présence de différentes quantités de zirconium. Les analyses de rayons X mettent<br />en évidence les particules qui formant ce matériau et l'influence du zirconium sur la forme de<br />cette particule. La spectroscopie dans la région de l'infrarouge a permis l'étude des liaisons<br />caractéristiques du matériau et les modifications structurelles liées à l'ajout de la phase<br />inorganique. Les caractéristiques du matériau ont été analysées par résonance magnétique<br />nucléaire. Les caractéristiques spectroscopiques du matériau sont détaillées, notamment la<br />luminescence intrinsèque du matériau et l'influence du zirconium. On montre que<br />l'introduction de l'ion europium confère de nouvelles propriétés et permet aussi une évaluation<br />structurelle complémentaire du matériau. Diverses applications du matériau étudié sous la<br />forme de couches minces sont présentées. Nous avons obtenu des réseaux de diffraction par<br />holographie, par lithographie, et également un effet laser à contre-réaction répartie dans des<br />films dopés avec la rhodamine 6G.

A variety of “clickable” self-assembling peptide-amphiphile hydrogel systems are reported. Covalently linked hydrogels were prepared using alkyne-azide “click” chemistry and thiolene photochemistry, which were used in combination with short self-assembling peptideamphiphile compounds. For alkyne-azide “click” hydrogels, samples were formed from a mixture of two peptideamphiphiles which were separately disubstituted with alkyne or azide functionalised amino acids. This allowed for production of an extensively triazole-linked hydrogel product when gelation was performed in combination with the appropriate “click” pre-catalyst and reductant. For thiol-ene photochemical hydrogels samples were formed from a mixture of two peptideamphiphiles which were separately disubstituted with cysteine or Alloc-protected lysine. UV exposure was used to catalyse the covalent linking of the asembled hydrogel. Michael addition thiol-ene reactions were also investigated as a potential covalent linking method. A number of model reactions were attempted on specially synthesised amino acids. Results were promising, but a number of difficulties were encountered which made them unsuitable for incorporation in a hydrogel system. The hydrogel samples produced were all found to be viscoelastic hydrogels through analysis by rheological methods. A variation in the stiffness of the samples was observed, with samples having Young’s modulus values in the soft to intermediate range when compared to that of various tissues. SEM analysis indicated the hydrogels exhibited a fibrous nanostructure. The biological activity of the hydrogel samples was investigated by 2D seeding of cells on hydrogel samples. A LIVE/DEAD assay was performed which indicated hydrogel samples were able to support cell attachment and growth in vitro.

I developed a system to release multiple growth factors from PEGylated fibrin gels with varying profiles to induce vasculogenesis from embedded human MSCs. Zero-order release can be obtained by conjugating a growth factor with a homobifunctional, amine-reactive, PEG derivative. Growth factors can be entrapped during thrombin-mediated crosslinking and released rapidly. Growth factors with physical affinity for fibrinogen or fibrin can be sequestered within the matrix and released via degradation and/or disassociation. PDGF-BB was loaded via entrapment while TGF-β1 was sequestered through a combination of physical affinity and conjugation. The affinity of TGF-β1 and fibrinogen had never been previously examined or quantified. I aimed to determine the Ka and Kd between TGF-β1 and fibrinogen through a variety of assays. Binding ELISAs were developed for TGF-β1 and fibronectin, a protein associated with fibrin gels, and TGF-β1 and fibrinogen. However, background was high due to insufficient blocking agents. Other assays explored included western blots, surface plasmon resonance, and radiolabeled TGF-β1 with limited success. The affect of TGF-β1 on human MSC differentiation towards vascular cell phenotypes was examined both in 2D and fibrin gels embedded with MSCs. With exposure to TGF-β1, MSC proliferation was significantly inhibited in both 2D and within fibrin gels indicating that loaded TGF-β1 maintained bioactivity for at least 7 days. Gene expression of MSCs exposed to TGF-β1 demonstrated inhibited endothelial cell differentiation and stimulated smooth muscle cell differentiation. However, confocal and light microscopy indicated that endothelial cell differentiation is maintained with TGF-β1 loaded PEGylated fibrin gels. The system developed is highly modular and can be applied to other tissue engineering systems. Furthermore, other growth factors could be incorporated to promote vascular cell differentiation. / text

Les " gels attractifs " constituent une catégorie particulière de fluides complexes. Ces gels sont formés à partir d'une suspension de particules attractives en faible concentration volumique. La microstructure du gel est très facilement modifiée par l'application d'une contrainte. Ainsi, il est possible de structurer ces gels par un cisaillement dans une géométrie suffisamment confinée. Nous avons étudié en détail ce phénomène dans des gels de noirs de carbone ainsi que dans des suspensions de billes de verre dans de l'huile rendues attractives par la présence d'une faible quantité d'eau. Nous avons reproduit ce phénomène dans des simulations numériques de dynamique moléculaire, ce qui permet d'étudier les conditions nécessaires à l'apparition de telles structures. Enfin, en géométrie peu confinée, le mécanisme de rupture et d'écoulement de ces gels en volume est complexe puisque leur rupture est en perpétuelle compétition avec leurcinétique de reformation. Nous avons étudié la rupture des gels de noir de carbone en couplant des techniques classiques de rhéologie avec une technique de mesure locale de déplacement par ultrasons. Ces expériences nous ont permis d'établir un lien entre le comportement global du matériau (sa rhéologie macroscopique) et la dynamique locale de fluidification.

<p>Even though women make up over half the population in the United States, medical advancements in areas of women's health have typically lagged behind the rest of the medical field. Specifically, two major threats to women's reproductive health include human immunodeficiency virus (HIV), and cervical cancer with accompanying human papillomavirus (HPV) infection. This dissertation presents the development and application of two novel optical imaging technologies aimed at improving these aspects of women's reproductive health.</p><p>The presented work details the instrumentation development of a probe-based, dual-modality optical imaging instrument, which uses simultaneous imaging of fluorimetry and multiplexed low coherence interferometry (mLCI) to measure in vivo microbicide gel thickness distributions. The study explores the optical performance of the device and provides proof of concept measurements on a calibration socket, tissue phantom, and in vivo human data. Once the instrument is fully characterized, it is applied in a clinical trial in which in vivo human vaginal gel thickness distributions. The gel distribution data obtained by the modalities are compared in order to assess the ability of mLCI making accurate in vivo measurements. Differences between the fluorimetry and mLCI modalities are then exploited in order to show a methodology for calculating the extent of microbicide gel dilution with the dual-modality instrument data.</p><p>Limitations in cervical cancer screening are then addressed as angle-resolved low coherence interferometry (a/LCI) is used in an ex vivo pilot study to assess the feasibility of a/LCI in identifying dysplasia in cervical tissues. The study found that the average nuclear diameter found by a/LCI in the basal layer of ectocervical epithelium showed a statistically significant increase in size in dysplastic tissue. These results indicate that a/LCI is capable of identifying cervical dysplasia in ectocervical epithelium. The results of the work presented in this dissertation show that dual-modality optical imaging with fluorimetry and mLCI, and the a/LCI technique show promise in advancing technologies that are used in the field of women's reproductive health.</p> / Dissertation